Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Application of Phthalazine Derivatives in Treating Hepatic Fibrosis

A technology for liver fibrosis and derivatives, which is applied in the field of phthalazine derivatives for the treatment of liver fibrosis diseases, can solve the problems that the targeted treatment of fibrosis diseases has not achieved satisfactory results, and achieve the effect of improving liver fibrosis.

Active Publication Date: 2022-05-24
NANJING UNIV
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Targeted treatment of fibrotic diseases has not yet achieved satisfactory results

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Application of Phthalazine Derivatives in Treating Hepatic Fibrosis
  • Application of Phthalazine Derivatives in Treating Hepatic Fibrosis
  • Application of Phthalazine Derivatives in Treating Hepatic Fibrosis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Synthesis of T-5-9:

[0041]

[0042]

[0043]

[0044] Wherein: Boc is tert-butoxycarbonyl, PyBOP is 1H-benzotriazol-1-yloxytripyrrolidinyl hexafluorophosphate; DIEA is N,N -Diisopropylethylamine; (Cl 3 CO) 2 CO is triphosgene.

[0045] 4-((4-((2-Fluorophenyl)carbamoyl)phenyl)carbamoyl)piperazine-1-carboxylate tert-butyl ester (2)

[0046] The 4-amino- N -(2-Fluorophenyl)benzamide (1) (4.75 g, 20.64 mmol) was dissolved in 30 mL of anhydrous dichloromethane, at room temperature, DIEA (7.19 mL, 41.28 mmol) and triphosgene (2.04 g, 6.88 mmol) in dichloromethane solution (20 mL), cooled to 0 °C and reacted for 3 hours, then added N -Boc-piperazine (5.77 g, 30.96 mmol), stirred at room temperature overnight, TLC detected that the raw material reacted completely, filtered, and the filtrate was concentrated to obtain a crude product, which was separated by column chromatography (eluent: dichloromethane: methanol=50:1 ) to obtain 7.12 g of a yellow solid with a...

Embodiment 2

[0055] Human semi-activated hepatic stellate cell line LX-2 cell assay

[0056] In this example, the LX-2 cell culture method: LX-2 cells were taken out from the -80 ℃ refrigerator, and the DMEM medium containing 10% fetal bovine serum was used in 10 cm 2 In a petri dish, 37 °C, 5% CO 2 Culture in the incubator, change the medium, passage, and take 3 to 6 passages for experiments.

[0057] 1. Western Blot experiment

[0058] Human semi-activated hepatic stellate cells LX-2 (5*10 5 (1 / well), and set up ① blank control group, ② TGF-β stimulation group, ③ T-5-9 (0.1 μM) group, ④ T-5-9 (1 μM) group, and ⑤ T-5-9 (10 μM) group. When the cell density in the well was 70%, the cells were treated as shown in Table 1. After 24 h, the lysed protein was quantitatively collected, and Western blot was used to detect the expression of Collagen I protein in LX-2. The expression of Collagen I in the stimulation group and the drug-added group was tested to test whether T-5-9 could inhibit t...

Embodiment 3

[0078] Anti-hepatic fibrosis animal test

[0079] The modeling method of the mouse liver fibrosis disease model in this example: 24 male mice (6-week-old, weighing 18-22 grams) were randomly divided into 4 groups, with 6 mice in each group. By injecting 10% carbon tetrachloride (CCl 4 , 0.5 ml / 100 g body weight) induced liver fibrosis in wild-type mice for 8 weeks (three times a week). The mice in the control group were injected with the same amount of olive oil instead of carbon tetrachloride; the mice in the model group were injected with carbon tetrachloride; the mice in the positive drug group were injected with CCl 4 , and given colchicine (0.1 mg / kg, once a day, week 5-8); mice in the treatment group were injected with CCl intraperitoneally 4 , and given T-5-9 (12.5mg / kg, once a day, the 5th to 8th week); the follow-up experiments and the attached drawings were named as: ① control group, ② model group, ③ positive drug group, ④ T-5 -9 groups. Blood and liver samples f...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses the use of phthalazine derivatives for treating liver fibrosis diseases, and relates to the field of biomedicine, in particular to the use of phthalazine derivatives represented by compound (I) for treating liver fibrosis diseases. The pharmacodynamic test of the present invention proves that compound (I) can inhibit the activation of hepatic stellate cells caused by TGF-β, and has obvious improvement effect on liver fibrosis in carbon tetrachloride model mice. The fibrosis has an inhibitory effect and can be used for the treatment of liver fibrosis, and the compound (I) can be used to prepare a drug for the treatment of liver fibrosis. (I).

Description

technical field [0001] The invention relates to the field of medicine, in particular to the use of phthalazine derivatives for treating liver fibrosis diseases. Background technique [0002] Chinese patent CN201810140689.6 discloses a class containing phthalazine-1 (2 H )-ketone structure compound, and it is disclosed that this kind of compound has PARP (poly(ADP-ribose) polymerase) inhibitory effect, so it has anti-tumor activity. Efficacy of tumor and the effect of reducing dose and toxicity. In the base excision repair pathway, PARP is a key DNA repair enzyme that regulates apoptosis and maintains genome stability. PARP inhibitors impede the DNA repair process by affecting PARP function, resulting in the death of cells lacking homologous recombination repair. In recent years, PARP has been extensively studied as an anti-tumor target. Olaparib is the first marketed PARP inhibitor for the treatment of recurrent epidermal ovarian cancer, fallopian tube cancer, and primar...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/502A61P1/16
Inventor 徐强徐忆竹吴兴新黄磊翟冰新朱启华
Owner NANJING UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com